Over the past few years there has been considerable interest in clinical applications of EIT, and such applications have extended to areas such as imaging changes in the thorax during breathing, in the stomach during gastric emptying and in the heart during intraventricular hemorrhage. EIT involves the application of spaced electrodes to the skin surface of a body under investigation, usually in the form of a belt around the body such that the electrodes lie in the plane of the body to be investigated. In a typical biomedical EIT system, low voltage alternating electrical current is applied between two neighboring electrodes (known as a drive pair) and the resulting potentials measured between pairs (known as driven pairs) of all the remaining electrodes. The potentials are recorded and the sequence repeated for all the other drive pairs, giving a matrix of measured impedance signal values. For example, the use of 16 electrodes provides a total of 104 independent impedance measurements. Using known reconstruction techniques this matrix can be processed by appropriate computer hardware to regenerate an image of impedance within the body plane. EIT methods and equipment have undergone considerable development and by making use of techniques such as parallel data collection and noise reduction, real time systems are now available capable of providing clinically useful images of dynamic phenomena. The basis of EIT is described in more detail in the paper "Applied Potential Tomography", Barber & Brown, 1984, J. Phys. E: Sci. Instrum., 17, 723-733. It is to be noted that neither the drive pair nor the receive pair need to comprise two adjacent electrodes, and in some cases a diametric drive pair and/or receive pair may offer certain advantages for clinical measurements.
One potentially interesting area for application of EIT techniques is in the clinical neurosciences, where scalp measurements are used to obtain images of functional changes in the human or animal brain. It is possible with existing equipment to form images of neural functional activity, such as that associated with stroke or spreading depression in a patient, due to the fact that cell swelling within the cortex of such subjects produces impedance increases of up to 30% ("Electrical impedance tomography with cortical or scalp electrodes during global cerebral ischaemia in the anaesthetised rat", D S Holder, Clin. Phys. Physiol. Meas. 1989, Vol. 13, No. 1, 87-98, and "Imaging of cortical spreading depression by EIT: Implications for localization of epileptic foci", K Boone, A M Lewis and D S Holder, Physiol. Meas. 15 (1994) A189-A198).
It has also been suggested that the much smaller changes in impedance during neuronal discharge might be measured by EIT techniques. ("Impedance changes during evoked nervous activity in human subjects: implications for the application of applied potential tomography (APT) to imaging neuronal discharge", D. S. Holder, Clin. Phys. Physiol. Meas. 1989, Vol. 10, No. 3, 267-274). The principle of this application is that the impedance of the neuronal membranes is known to fall during the action potential or during the sub-threshold depolarizations which accompany synaptic activity, and there may be other related effects such as the movement of ions between intra- and extra-cellular compartments. By use of scalp electrodes, changes in impedance taking place in the brain may be recorded and used to image the progress of information along circuits within the brain. For example, the brain may be stimulated by a visual signal and EIT images subsequently reconstructed for each millisecond or so of the recording window, thus enabling the resultant action potential processes to be tracked along their pathways in the subject's brain. There is no established technique which at present permits accurate imaging of neuronal depolarization with millisecond or sub-millisecond time resolution. MRI and PET techniques produce images of cerebral activity, but these are related to metabolic recovery processes, which occur over seconds or minutes.
One of the problems with this approach is that the impedance changes associated with action potentials are generally very small and very rapid. Even if there is a substantial decrease in the resistance of the neuronal membranes themselves when they depolarize, the impedance of the tissue as a whole may not change in the same proportion, because the amount of current that enters the neuronal axoplasm depends more on the absolute impedance of the nerve axons and their geometry than it does on the membrane impedance. One study has estimated that the changes in impedance are, at most, between 0.1 and 1% of the resting impedance, depending on the area of the brain concerned. It is therefore clear that the resolution and sensitivity of an EIT system will need to be very high to accurately image such small changes using measurements taken using scalp electrodes, and currently available devices are not capable of producing such images.
Investigations into the above-mentioned technique of imaging action potentials have been carried out using a prototype system employing square wave excitation of 50 .mu.A at 5 Hz applied to a saline phantom. The square wave signal was chosen because the capacitive properties of the cell membranes mean that the high frequencies used in conventional EIT systems are generally unsuitable. The resulting inter-electrode potentials were sampled at a rate of 4000 frames per second and 100 sets of frames were averaged to produce the results. The results of the experiment showed a signal-to-noise ratio of 40-50 dB and reciprocity errors of 10%-20%. Images of discrete resistivity changes of less than 10% could be obtained but with significant systematic errors. The prototype was thus found to be unsuitable for neurophysiological imaging.
One of the problems of the prototype system has been that of noise. With the square wave signal used the amplifiers will detect a higher level of extraneous noise than would be the case with an AC system. 50 Hz mains interference lies within the recording bandwidth, as does intrinsic EEG activity associated with the action potentials. Previous systems have attempted to minimize the noise effects by filtering or averaging, but such attempts have met with limited success.